Pediatric MATCH: Targeted Therapy Directed by Genetic Testing in Treating Pediatric Patients With Advanced Refractory Solid Tumors or Lymphomas - Full Text View

Purpose

This screening and multi-sub-study phase II trial studies how well treatment that is directed by genetic testing works in pediatric patients with solid tumors or lymphomas that have progressed following at least one line of standard systemic therapy and/or for which no standard treatment exists that has been shown to prolong survival. Genetic tests look at the unique genetic material (genes) of patients' tumor cells. Patients with genetic changes or abnormalities (mutations) may benefit more from treatment which targets their tumor's particular genetic mutation, and may help doctors plan better treatment for patients with solid tumors or lymphomas.

Condition	Intervention	Phase
Histiocytic Sarcoma Juvenile Xanthogranuloma Langerhans Cell Histiocytosis Lymphoma Recurrent Central Nervous System Neoplasm Recurrent Malignant Solid Neoplasm Refractory Central Nervous System Neoplasm Refractory Malignant Solid Neoplasm	Drug: ALK Inhibitor X-396 Procedure: Biopsy Procedure: Biospecimen Collection Other: Laboratory Biomarker Analysis Procedure: Mutation Carrier Screening Drug: Olaparib Other: Pharmacological Study Drug: PI3K/mTOR Inhibitor LY3023414 Drug: Selumetinib Sulfate Drug: Tazemetostat Drug: Trk Inhibitor LOXO-101 Drug: Vemurafenib	Phase 2


Study Type:	Interventional
Study Design:	Allocation: Non-Randomized Intervention Model: Parallel Assignment Masking: No masking Primary Purpose: Treatment
Official Title:	NCI-COG Pediatric MATCH (Molecular Analysis for Therapy Choice) Screening Protocol

Resource links provided by NLM:

MedlinePlus related topics: Genetic Testing

Genetic and Rare Diseases Information Center resources: Lymphosarcoma Soft Tissue Sarcoma Langerhans Cell Histiocytosis Lipogranulomatosis

U.S. FDA Resources

Further study details as provided by National Cancer Institute (NCI):

Primary Outcome Measures:

Objective response rate (complete response/partial response) assessed according to Response Evaluation Criteria in Solid Tumors version 1.1 [ Time Frame: Up to 4 years ]
Response rates will be calculated as the percent of evaluable patients who are responders, and confidence intervals will be constructed using the Wilson score interval method.

Secondary Outcome Measures:

Incidence of research biopsy related target toxicity as defined as any >= grade 3 toxicity or complication that is probably or definitely attributable to any biopsy-related anesthesia or imaging procedures that occurs within 14 days of research [ Time Frame: Up to 14 days ]
Incidence of research biopsy related target toxicity will be assessed.
Incidence of toxicity assessed by the National Cancer Institute Common Terminology Criteria for Adverse Events version 4.0 [ Time Frame: Up to 4 years ]
Toxicity tables will be constructed to summarize the observed incidence by type of toxicity and grade. Toxicity information recorded will include the type, severity, time of onset, time of resolution, and the probable association with the study regimen.
Progression free survival [ Time Frame: From the initiation of protocol treatment to the occurrence of any of the following events: disease progression or disease recurrence or death from any cause, assessed up to 4 years ]
Estimated using the Kaplan-Meier method along with confidence intervals.

Other Outcome Measures:

Diagnostic yield of relapsed tumor sequencing on National Cancer Institute pediatric molecular analysis for therapy choice [ Time Frame: Up to 4 years ]
A descriptive analysis will be performed and will be summarized with simple summary statistics. This analysis will be descriptive in nature. Will be compared with pre-treatment tumor sequencing using patient-matched formalin-fixed paraffin-embedded specimens.
Feasibility of using plasma-based testing methods for detection of the tumor mutations identified by National Cancer Institute pediatric molecular analysis for therapy choice tumor sequencing [ Time Frame: Up to 4 years ]
A descriptive analysis will be performed and will be summarized with simple summary statistics. This analysis will be descriptive in nature.
Frequency of germline cancer susceptibility mutations in children with relapsed solid tumors and lymphomas [ Time Frame: Up to 4 years ]
A descriptive analysis will be performed and will be summarized with simple summary statistics. This analysis will be descriptive in nature.
Genomic landscape of relapsed pediatric solid tumors and lymphomas [ Time Frame: Up to 4 years ]
A descriptive analysis will be performed and will be summarized with simple summary statistics. This analysis will be descriptive in nature.
Potential predictive biomarkers (other than the genomic alteration for which study treatment was assigned) analyzed by additional genomic, transcriptomic, and proteomic testing platforms [ Time Frame: Up to 4 years ]
A descriptive analysis will be performed and will be summarized with simple summary statistics. This analysis will be descriptive in nature.
Spectrum of germline cancer susceptibility mutations in children with relapsed solid tumors and lymphomas [ Time Frame: Up to 4 years ]
A descriptive analysis will be performed and will be summarized with simple summary statistics. This analysis will be descriptive in nature.


Estimated Enrollment:	568
Anticipated Study Start Date:	July 6, 2017
Estimated Study Completion Date:	December 31, 2021
Estimated Primary Completion Date:	December 31, 2021 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Experimental: Subprotocol A (NTRK1, NTRK2, or NTRK3 gene fusion) Patients with a NTRK1, NTRK2, or NTRK3 gene fusion receive Trk inhibitor LOXO-101 orally (PO) twice daily (BID) on days 1-28. Courses repeat every 28 days for 2 years in the absence of disease progression or unacceptable toxicity.	Procedure: Biopsy Undergo biopsy Other Name: Bx Procedure: Biospecimen Collection Undergo collection of blood Other: Laboratory Biomarker Analysis Undergo molecular analysis Procedure: Mutation Carrier Screening Undergo tumor tissue mutation screening Other: Pharmacological Study Correlative studies Drug: Trk Inhibitor LOXO-101 Given PO Other Name: LOXO-101
Experimental: Subprotocol C (EZH2, SMARCB1, or SMARCA4 gene alteration) Patients with an EZH2, SMARCB1, or SMARCA4 gene alteration receive tazemetostat PO BID on days 1-28. Courses repeat every 28 days for 2 years in the absence of disease progression or unacceptable toxicity.	Procedure: Biopsy Undergo biopsy Other Name: Bx Procedure: Biospecimen Collection Undergo collection of blood Other: Laboratory Biomarker Analysis Undergo molecular analysis Procedure: Mutation Carrier Screening Undergo tumor tissue mutation screening Drug: Tazemetostat Given PO Other Names: E7438 EPZ-6438 EPZ6438
Experimental: Subprotocol D (TSC1, TSC2, or PI3K/mTOR activating mutation) Patients with a deleterious TSC1 or TSC2 gene mutation, and/or other PI3K/MTOR activating mutation receive PI3K/mTOR inhibitor LY3023414 PO BID on days 1-28. Courses repeat every 28 days for 2 years in the absence of disease progression or unacceptable toxicity.	Procedure: Biopsy Undergo biopsy Other Name: Bx Procedure: Biospecimen Collection Undergo collection of blood Other: Laboratory Biomarker Analysis Undergo molecular analysis Procedure: Mutation Carrier Screening Undergo tumor tissue mutation screening Other: Pharmacological Study Correlative studies Drug: PI3K/mTOR Inhibitor LY3023414 Given PO Other Names: LY 3023414 LY-3023414 LY3023414
Experimental: Subprotocol E (activating MAPK pathway gene alteration) Patients with an activating MAPK pathway gene alteration receive selumetinib sulfate PO BID on days 1-28. Courses repeat every 28 days for 2 years in the absence of disease progression or unacceptable toxicity.	Procedure: Biopsy Undergo biopsy Other Name: Bx Procedure: Biospecimen Collection Undergo collection of blood Other: Laboratory Biomarker Analysis Undergo molecular analysis Procedure: Mutation Carrier Screening Undergo tumor tissue mutation screening Drug: Selumetinib Sulfate Given PO Other Names: AZD-6244 Hydrogen Sulfate AZD6244 Hydrogen Sulfate AZD6244 Hydrogen Sulphate Selumetinib Sulphate
Experimental: Subprotocol F (ALK or ROS1 fusion or ALK missense mutation) Patients with an ALK gene fusion, ROS1 gene fusion, or ALK missense mutation receive ALK Inhibitor X-396 PO BID on days 1-28. Courses repeat every 28 days for 2 years in the absence of disease progression or unacceptable toxicity.	Drug: ALK Inhibitor X-396 Given PO Other Names: Anaplastic Lymphoma Kinase Inhibitor X-396 X-396 Procedure: Biopsy Undergo biopsy Other Name: Bx Procedure: Biospecimen Collection Undergo collection of blood Other: Laboratory Biomarker Analysis Undergo molecular analysis Procedure: Mutation Carrier Screening Undergo tumor tissue mutation screening Other: Pharmacological Study Correlative studies
Experimental: Subprotocol G (BRAF V600 gene mutation) Patients with a BRAF V600 gene mutation receive vemurafenib PO BID on days 1-28. Courses repeat every 28 days for 2 years in the absence of disease progression or unacceptable toxicity.	Procedure: Biopsy Undergo biopsy Other Name: Bx Procedure: Biospecimen Collection Undergo collection of blood Other: Laboratory Biomarker Analysis Undergo molecular analysis Procedure: Mutation Carrier Screening Undergo tumor tissue mutation screening Drug: Vemurafenib Given PO Other Names: BRAF (V600E) kinase inhibitor RO5185426 BRAF(V600E) Kinase Inhibitor RO5185426 PLX-4032 PLX4032 RG 7204 RG7204 RO 5185426 Zelboraf
Experimental: Subprotocol H (deleterious DNA damage repair gene alteration) Patients with a deleterious DNA damage repair gene alteration receive olaparib PO BID on days 1-28. Courses repeat every 28 days for 2 years in the absence of disease progression or unacceptable toxicity.	Procedure: Biopsy Undergo biopsy Other Name: Bx Procedure: Biospecimen Collection Undergo collection of blood Other: Laboratory Biomarker Analysis Undergo molecular analysis Procedure: Mutation Carrier Screening Undergo tumor tissue mutation screening Drug: Olaparib Given PO Other Names: AZD2281 KU-0059436 Lynparza PARP Inhibitor AZD2281 Other: Pharmacological Study Correlative studies

Show Detailed Description

Eligibility


Ages Eligible for Study:	12 Months to 21 Years (Child, Adult)
Sexes Eligible for Study:	All
Accepts Healthy Volunteers:	No

Criteria

Inclusion Criteria:

ELIGIBILITY CRITERIA FOR ENROLLMENT ONTO APEC1621SC: Patients with recurrent or refractory solid tumors (including lymphomas, histiocytoses [e.g. Langerhans cell histiocytosis (LCH), juvenile xanthogranuloma (JXG), histiocytic sarcoma], and central nervous system [CNS] tumors) are eligible; patients must have had histologic verification of malignancy at original diagnosis or relapse except in patients with intrinsic brain stem tumors, optic pathway gliomas, or patients with pineal tumors and elevations of cerebrospinal fluid (CSF) or serum tumor markers including alpha-fetoprotein or beta-HCG
ELIGIBILITY CRITERIA FOR ENROLLMENT ONTO APEC1621SC: Patients must have a formalin fixed paraffin embedded (FFPE) tumor sample available for MATCH study testing from a biopsy or surgery that was performed at any point after initial tumor recurrence/progression, or be planned to have a procedure to obtain such a sample that is considered to be of potential benefit by the treating clinicians; a tumor sample from a clinically performed diagnostic (pre-treatment) biopsy will be acceptable for enrollment onto Pediatric MATCH for children with diffuse intrinsic pontine gliomas (DIPG, brainstem gliomas)
ELIGIBILITY CRITERIA FOR ENROLLMENT ONTO APEC1621SC: Karnofsky >= 50% for patients > 16 years of age and Lansky >= 50 for patients =< 16 years of age); Note: neurologic deficits in patients with CNS tumors must have been stable for at least 7 days prior to study enrollment; patients who are unable to walk because of paralysis, but who are up in a wheelchair, will be considered ambulatory for the purpose of assessing the performance score
GENERAL INCLUSION CRITERIA FOR SUBPROTOCOLS:

NOTE: patient does not need to meet all subprotocol criteria at time of enrollment onto the APEC1621 screening protocol, but will need to meet all criteria prior to enrollment on any assigned treatment subprotocol; patients must be enrolled onto a subprotocol within 8 weeks (56 days) of treatment assignment

GENERAL INCLUSION CRITERIA FOR SUBPROTOCOLS: Karnofsky >= 50% for patients > 16 years of age and Lansky >= 50 for patients =< 16 years of age); Note: neurologic deficits in patients with CNS tumors must have been stable for at least 7 days prior to study enrollment; patients who are unable to walk because of paralysis, but who are up in a wheelchair, will be considered ambulatory for the purpose of assessing the performance score
GENERAL INCLUSION CRITERIA FOR SUBPROTOCOLS: At the time of treatment with subprotocol specified therapy, the patients must have radiographically measurable disease; patients with neuroblastoma who do not have measurable disease but have metaiodobenzylguanidine (MIBG) positive (+) evaluable are eligible; measurable disease in patients with CNS involvement is defined as tumor that is measurable in two perpendicular diameters on magnetic resonance imaging (MRI) and visible on more than one slice
- Note: The following do not qualify as measurable disease:
  - malignant fluid collections (e.g., ascites, pleural effusions)
  - bone marrow infiltration except that detected by MIBG scan for neuroblastoma
  - lesions only detected by nuclear medicine studies (e.g., bone, gallium or positron emission tomography [PET] scans) except as noted for neuroblastoma
  - elevated tumor markers in plasma or CSF
  - previously radiated lesions that have not demonstrated clear progression post radiation
  - leptomeningeal lesions that do not meet the measurement requirements for Response Evaluation Criteria in Solid Tumors (RECIST) 1.1.
GENERAL INCLUSION CRITERIA FOR SUBPROTOCOLS: At the time of enrollment onto a subprotocol, the following general criteria for initiation of therapy will be required:
- Patients must have fully recovered from the acute toxic effects of all prior anticancer therapy and must meet the following minimum duration from prior anticancer directed therapy prior to enrollment to the subprotocol; if after the required timeframe, the numerical eligibility criteria are met, e.g. blood count criteria, the patient is considered to have recovered adequately
  - Cytotoxic chemotherapy or other anticancer agents known to be myelosuppressive: See https://members.childrensoncologygroup.org/Disc/devtherapeutics/default.asp for commercial and phase 1 investigational agent classifications; for agents not listed, the duration of this interval must be discussed with the study chair and the study-assigned research coordinator prior to enrollment
    - >= 21 days after the last dose of cytotoxic or myelosuppressive chemotherapy (42 days if prior nitrosourea)
  - Anticancer agents not known to be myelosuppressive (e.g. not associated with reduced platelet or absolute neutrophil counts [ANC]): >= 7 days after the last dose of agent; See https://members.childrensoncologygroup.org/Disc/devtherapeutics/default.asp for commercial and phase 1 investigational agent classifications; for agents not listed, the duration of this interval must be discussed with the study chair and the study-assigned research coordinator prior to enrollment
  - Antibodies: >= 21 days must have elapsed from infusion of last dose of antibody, and toxicity related to prior antibody therapy must be recovered to grade =< 1
  - Corticosteroids: If used to modify immune adverse events related to prior therapy, >= 14 days must have elapsed since last dose of corticosteroid
  - Hematopoietic growth factors: >= 14 days after the last dose of a long-acting growth factor (e.g. Neulasta) or 7 days for short-acting growth factor; for agents that have known adverse events occurring beyond 7 days after administration, this period must be extended beyond the time during which adverse events are known to occur; the duration of this interval must be discussed with the study chair and the study-assigned research coordinator
  - Interleukins, interferons and cytokines (other than gematopoietic growth factors): >= 21 days after the completion of interleukins, interferon or cytokines (other than hematopoietic growth factors)
  - Stem cell Infusions (with or without TBI):
    - Allogeneic (non-autologous) bone marrow or stem cell transplant, or any stem cell infusion including DLI or boost infusion: >= 84 days after infusion and no evidence of GVHD.
    - Autologous stem cell infusion including boost infusion: >= 42 days
  - Cellular therapy: >= 42 days after the completion of any type of cellular therapy (e.g. modified T cells, NK cells, dendritic cells, etc.)
  - X-ray therapy (XRT)/External Beam Irradiation including Protons: >= 14 days after local XRT; >= 150 days after TBI, craniospinal XRT or if radiation to >= 50% of the pelvis; >= 42 days if other substantial bone marrow (BM) radiation; note: radiation may not be delivered to "measurable disease" tumor site(s) being used to follow response to subprotocol treatment
  - Radiopharmaceutical therapy (e.g., radiolabeled antibody, 131I-MIBG): >= 42 days after systemically administered radiopharmaceutical therapy
GENERAL INCLUSION CRITERIA FOR SUBPROTOCOLS: For patients with solid tumors without known bone marrow involvement:
- Peripheral absolute neutrophil count (ANC) >= 1000/mm^3
- Platelet count >= 100,000/mm^3 (transfusion independent, defined as not receiving platelet transfusions for at least 7 days prior to enrollment)
GENERAL INCLUSION CRITERIA FOR SUBPROTOCOLS: Patients with known bone marrow metastatic disease will be eligible for study provided they meet the blood counts (may receive transfusions provided they are not known to be refractory to red cell or platelet transfusions); these patients will not be evaluable for hematologic toxicity
GENERAL INCLUSION CRITERIA FOR SUBPROTOCOLS: Creatinine clearance or radioisotope glomerular filtration rate (GFR) >= 70ml/min/1.73 m^2 or a serum creatinine based on age/gender as follows:
- Age: 1 to < 2 years; maximum serum creatinine (mg/dL): male 0.6; female 0.6
- Age: 2 to < 6 years; maximum serum creatinine (mg/dL): male 0.8; female 0.8
- Age: 6 to < 10 years; maximum serum creatinine (mg/dL): male 1; female 1
- Age: 10 to < 13 years; maximum serum creatinine (mg/dL): male 1.2; female 1.2
- Age: 13 to < 16 years; maximum serum creatinine (mg/dL): male 1.5; female 1.4
- Age: >= 16 years; maximum serum creatinine (mg/dL): male 1.7; female 1.4
GENERAL INCLUSION CRITERIA FOR SUBPROTOCOLS: Bilirubin (sum of conjugated + unconjugated) =< 1.5 x upper limit of normal (ULN) for age
GENERAL INCLUSION CRITERIA FOR SUBPROTOCOLS: serum glutamate pyruvate transaminase (SGPT) (alanine transferase [ALT]) =< 135 U/L (for the purpose of this study, the ULN for SGPT is 45 U/L)
GENERAL INCLUSION CRITERIA FOR SUBPROTOCOLS: Patients must be able to swallow intact capsules/tablets, unless otherwise specified in the subprotocol to which they are assigned
GENERAL INCLUSION CRITERIA FOR SUBPROTOCOLS: Agent specific limitations on prior therapy will be included with specific treatment subprotocols

Exclusion Criteria:

GENERAL EXCLUSION CRITERIA FOR SUBPROTOCOLS: Pregnant or breast-feeding women will not be entered on this study; pregnancy tests must be obtained in females who are post-menarcheal; males or females of reproductive potential may not participate unless they have agreed to use an effective contraceptive method
GENERAL EXCLUSION CRITERIA FOR SUBPROTOCOLS: Concomitant medications
- Corticosteroids: at the time of consent and enrollment to regimen specific subprotocols, patients receiving corticosteroids who have not been on a stable or decreasing dose of corticosteroid for at least 7 days prior to enrollment to the subprotocol will not be eligible; if used to modify immune adverse events related to prior therapy, >= 14 days must have elapsed since last dose of corticosteroid
- Investigational drugs: patients must meet criteria for prior therapy at the time of consent and enrollment to a subprotocol; other investigational agents may not be administered to patients while they are receiving study drug as part of a subprotocol
- Anticancer agents: patients must meet criteria for prior therapy at the time of consent and enrollment to a subprotocol; other investigational agents may not be administered to patients while they are receiving study drug as part of a subprotocol
- Anti-GVHD agents post-transplant: patients who are receiving cyclosporine, tacrolimus or other agents to prevent graft-versus-host disease post bone marrow transplant are not eligible
GENERAL EXCLUSION CRITERIA FOR SUBPROTOCOLS: Patients who have an uncontrolled infection are not eligible
GENERAL EXCLUSION CRITERIA FOR SUBPROTOCOLS: Patients who have had a prior solid organ transplant are not eligible
GENERAL EXCLUSION CRITERIA FOR SUBPROTOCOLS: Additional agent specific criteria will be included with specific treatment subprotocols

Contacts and Locations

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT03155620

Locations


United States, Pennsylvania
Childrens Oncology Group	Not yet recruiting
Philadelphia, Pennsylvania, United States, 19104
Contact: Donald W. Parsons 832-824-4643 dwparson@txch.org
Principal Investigator: Donald W. Parsons

Sponsors and Collaborators

National Cancer Institute (NCI)

Investigators


Principal Investigator:	Donald Parsons	Children's Oncology Group

More Information


Responsible Party:	National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:	NCT03155620 History of Changes
Other Study ID Numbers:	NCI-2017-00910 NCI-2017-00910 ( Registry Identifier: CTRP (Clinical Trial Reporting Program) ) Ped MATCH APEC1621 ( Other Identifier: Childrens Oncology Group ) Ped MATCH APEC1621 ( Other Identifier: CTEP ) U10CA180886 ( U.S. NIH Grant/Contract )
Study First Received:	May 15, 2017
Last Updated:	May 15, 2017


Studies a U.S. FDA-regulated Drug Product:		Yes
Studies a U.S. FDA-regulated Device Product:		No

Additional relevant MeSH terms:


Xanthogranuloma, Juvenile Lymphoma Neoplasms Histiocytosis Histiocytosis, Langerhans-Cell Nervous System Neoplasms Central Nervous System Neoplasms Histiocytic Sarcoma Neoplasms by Histologic Type Lymphoproliferative Disorders Lymphatic Diseases Immunoproliferative Disorders Immune System Diseases Lung Diseases, Interstitial Lung Diseases	Respiratory Tract Diseases Neoplasms by Site Nervous System Diseases Histiocytosis, Non-Langerhans-Cell Skin Diseases Histiocytic Disorders, Malignant Olaparib Everolimus Sirolimus Poly(ADP-ribose) Polymerase Inhibitors Enzyme Inhibitors Molecular Mechanisms of Pharmacological Action Antineoplastic Agents Immunosuppressive Agents Immunologic Factors

ClinicalTrials.gov processed this record on July 14, 2017